Maintained by Robin Tecon, microbiologist and postdoctoral researcher at the Swiss Federal Institute of Technology Zürich. This blog is about bacteria (and other microbes) and the scientists who study them.

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Sunday, February 23, 2014

Oceans, bacteria, and the quest for new drugs

We rely on
natural products in medicine: the vast majority of pharmaceutical drugs are
thus of plant or microbial origin. (The purely synthetic drugs, which have no
counterparts in the environment, are the exception rather than the rule.) To
name potent examples of natural products, take antibiotics (discovered in fungi
and bacteria), the anti-malaria drug artemisinin (isolated from sweet wormwood)
or simply aspirin (salicylic acid is present in willow bark). Many people, I
think, forget about this, as they oppose a so-called ‘natural’ medicine to a ‘chemical’
medicine (the pills you get from your doctor).

It is not
easy to find new active compounds, however, and much more difficult to test
them and turn them into a real medicine. The situation doesn’t look that good,
notably because of the high increase of antibiotic-resistant strains of
bacteria, and the paucity of new drugs available. A natural environment that
has long been recognized as a promising source of new chemicals is the largest
on Earth—oceans—, and many researchers are mining the sea in search of new
organisms and their specific biochemical abilities. For instance, the research
project PharmaSea, funded by the European Union, was launched in 2013 with the
goal of discovering new microbial organisms that could be the source of useful chemicals
for medicine or industry. This team of academics and industry researchers plan
to explore the deep bottom of the sea, looking for environments that are poorly
known and potentially harbor interesting organisms. Here’s an excerpt from the project
website:

“Marine organisms that live more than 6,000
meters below the sea level are considered to be an interesting source of novel
bioactive compounds as they survive under extreme conditions. "Trenches
are separated from each other and represent islands of diversity. They are not
connected to each other and life has evolved differently in each one",
explains Marcel Jaspars[PharmaSea project leader]. “

PharmaSea is an
ambitious project, and it may not be easy at all to get many new products out
of it, but the goal has to be praised, as we surely are in need of new
biochemicals, particularly new antibiotics.

Another
exciting example of ocean biodiscovery was recently published in the journal Nature. It is the collaboration of research
groups in Japan, Germany, USA and Switzerland, and led by Jörn Piel,
professor in the Institute of Microbiology at ETH Zürich. (A summary of the
findings was published on the ETH News website.) This team of scientists is
interested in a species of marine sponge, Theonella
swinhoei, which is known to produce many bioactive compounds (notably
polytheonamides). The sponge, however, is not producing these chemicals itself;
instead, symbiotic microorganisms are doing the job. It’s worth knowing that
most sponge species live in close association with a large consortium of many
diverse bacteria (not unlike the bacterial flora in our gut), and that most of
these bacteria are unknown to us and can’t even be grown in the laboratory.

The
group of Prof. Piel identified a new group of bacteria, living in symbiosis
with Theonella swinhoei, which is
responsible for the synthesis of most bioactive compounds in the sponge; they proposed
a new genus name (Entotheonella) and
even a new taxon (Tectomicrobia) to characterize these microorganisms. Many advanced
techniques were necessary for this breakthrough, including single-cell genome
analysis.

The
discovery of a new potent drug producer, as exciting as it is, is far from the
end of the story. One major issue is to extract enough material to pursue
clinical trials, something not easy with marine sponges, which at present
cannot be cultivated. What is more, most of these compounds are too complex to
be synthesized chemically. But if we could harness the biochemical ability of
the sponge microorganisms, outside of
their host, this would offer an alternative. That, unfortunately, is not
guaranteed to work, as microorganisms grown in pure cultures in the lab often
behave unpredictably (in that case, that could be by stopping
the production of bioactive compounds). A third route exists: using bioengineering
technology to transfer Entotheonella’s
ability to produce bioactive compounds in other, more amenable microorganisms
(say, yeast or E. coli). In other
words, it’s still a long way to the development of useful drugs from sponge
microbes. But, at least, there is a way.